Modulation of choline acetyltransferase synthesis by okadaic acid, a phosphatase inhibitor, and KN-62, a CaM kinase inhibitor, in NS-20Y neuroblastoma

被引:6
作者
Pahud, G
Bontron, S
Eder-Colli, L
机构
[1] Ctr Med Univ Geneva, APSIC, Dept Pharmacol, CH-1211 Geneva 4, Switzerland
[2] Ctr Med Univ Geneva, Dept Genet & Microbiol, CH-1211 Geneva, Switzerland
关键词
choline acetyltransferase; cholinergic neuroblastoma; phosphoprotein phosphatase; phosphoprotein kinase;
D O I
10.1016/S0197-0186(00)00064-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Choline-O-acetyltransferase (ChAT) is the enzyme which catalyses the biosynthesis of the neurotransmitter acetylcholine in cholinergic neurons. Here we show that in mouse cholinergic NS-20Y neuroblastoma cells cultured in the presence of either okadaic acid (serine/threonine phosphatases 1 and 2A inhibitor) or KN-62 (CaM kinase inhibitor) ChAT activity and mRNA either increased or decreased as a function of the drug concentration, respectively. After 24 h exposure, okadaic acid exerted a dramatic effect on cell morphology; cells became round and had no more neurites. On the contrary, KN-62 induced a slight morphological differentiation of the cells. The present results suggest that phosphatases 1 and 2A and CaM kinase could mediate regulation of ChAT gene expression. (C) 2000 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:75 / 82
页数:8
相关论文
共 21 条
[1]   NEUROTRANSMITTER SYNTHESIS BY NEUROBLASTOMA CLONES [J].
AMANO, T ;
NIRENBERG, M ;
RICHELSON, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1972, 69 (01) :258-+
[2]   MEMBRANE-BOUND CHOLINE-ACETYLTRANSFERASE IS A CELL-SURFACE MARKER OF THE DIFFERENTIATED NS-20Y CHOLINERGIC CELL-LINE [J].
BAROCHOVSKY, O ;
DOCHERTY, M ;
BRADFORD, HF .
NEUROSCIENCE LETTERS, 1988, 90 (03) :320-327
[3]   THE PHOSPHORYLATION OF CHOLINE-ACETYLTRANSFERASE [J].
BRUCE, G ;
HERSH, LB .
NEUROCHEMICAL RESEARCH, 1989, 14 (07) :613-620
[4]   Inhibitors of serine/threonine phosphatases increase membrane-bound choline acetyltransferase activity and enhance acetylcholine synthesis [J].
Cooke, LJ ;
Rylett, RJ .
BRAIN RESEARCH, 1997, 751 (02) :232-238
[5]   A RADIOCHEMICAL METHOD FOR ESTIMATION OF CHOLINE ACETYLTRANSFERASE [J].
FONNUM, F .
BIOCHEMICAL JOURNAL, 1966, 100 (02) :479-+
[6]   TRANSCRIPTIONAL ATTENUATION FOLLOWING CAMP INDUCTION REQUIRES PP-1-MEDIATED DEPHOSPHORYLATION OF CREB [J].
HAGIWARA, M ;
ALBERTS, A ;
BRINDLE, P ;
MEINKOTH, J ;
FERAMISCO, J ;
DENG, T ;
KARIN, M ;
SHENOLIKAR, S ;
MONTMINY, M .
CELL, 1992, 70 (01) :105-113
[7]  
INOUE H, 1995, J NEUROCHEM, V64, P985
[9]   2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN KILLS IMMATURE THYMOCYTES BY CA-2+-MEDIATED ENDONUCLEASE ACTIVATION [J].
MCCONKEY, DJ ;
HARTZELL, P ;
DUDDY, SK ;
HAKANSSON, H ;
ORRENIUS, S .
SCIENCE, 1988, 242 (4876) :256-259
[10]   TRANSCRIPTIONAL REGULATION OF CHOLINE-ACETYLTRANSFERASE GENE BY CYCLIC-AMP [J].
MISAWA, H ;
TAKAHASHI, R ;
DEGUCHI, T .
JOURNAL OF NEUROCHEMISTRY, 1993, 60 (04) :1383-1387